The long-term objective of the proposed research is to understand the cellular mechanisms that underlie vision. The premise underlying this application is that the remarkable adaptability of vision is based on the plasticity of intracellular signaling pathways in retinal neurons. The focus of the work will be to study the mechanisms that regulate the intracellular Ca2+ concentration and transmitter release in retinal rod and cone photoreceptor neurons. The proposed experiments combine electrophysiological, optical and immunocytochemical methods. Results obtained in these studies will help us select cellular targets for therapeutic interventions during retinal disease and blindness. Three specific aims are proposed: (1) to characterize Ca2+ regulation in photoreceptor inner segments; (2) to identify differences in Ca2+ homeostasis between rod and cone photoreceptor inner segments; and (3) to determine the relationship between [Ca2+]&#1110; and exocytosis in photoreceptors.